Table 1.

Clinical and molecular findings in the individuals with N-terminal FHF2A variants

Individual	1 (family A)	2 (family A)	3 (family B)	4 (family B)	5 (family C)	6 (family D)	7 (family E)
Age	15 y	13 y	19 y	12 y	2 y 3 m	5 y	5y 8 m
Sex	male	female	male	male	male	male	male
Variant	c.31C>T (p.Arg11Cys)	c.31C>T (p.Arg11Cys)	c.31C>T (p.Arg11Cys)	c.31C>T (p.Arg11Cys)	c.31C>T (p.Arg11Cys)	c.41G>C (p.Arg14Thr)	c.32G>C (p.Arg11Pro)
Inheritance	maternal gonadal mosaicisma	maternal gonadal mosaicisma	maternal somatic mosaicism	maternal somatic mosaicism	de novo	unknown	mosaic
OFC	−1.4 SD at 13 y 10 m	+0.8 SD at 6 y 9 m	−0.2 SD at 19 y	−1.4 SD at 12 y 5 m	−1.1 SD at 22 m	−2.5 SD at 5 y	−2.6 SD at 3 y 2 m
ID/DD	profound	severe	severe	severe	profound	severe	severe
Initial concerns	11 d, apneas, repetitive swallowing, head deviation, eye twitching	11 d, apneas, lip smacking, repetitive swallowing, eye deviation, facial twitching	4 w, apneas, stiffness	6 m, head and eye deviation, twitching	5 d, head and eye deviation, blinking, repetitive swallowing	1 d, apnea, cyanosis	6 m, focal sz
Epilepsy	focal sz at 2 m. generalized sz from 7 m	focal sz from 11 m. rarely generalized	focal sz at 2 m. flexor spasms from 6 m	focal sz at 6 m. generalized sz from 2.5 y, episodes of NCSE, tonic sz and vomiting currently	focal dyscognitive seizures	yes	focal sz at 6 m. also spasms, myoclonic sz, GTCS
EEG	multiple epileptogenic temporal foci, EIMFS considered	ictal EEG at 6 y 8 m, left fronto-temporal focus	hypsarrhythmia at 6 m. later EEG suggestive of LGS	hypsarrhythmia at 2.5 y, EEG at 11 y suggestive of LGS	multiple epileptogenic temporal foci, suggestive of LGS	n/k	atypical hypsarrhythmia and intermittent burst suppression at 23 m
Neurology	hypotonia, no hyperreflexia	normal tone and reflexes	low axial tone, mild limb hypertonia, no hyperreflexia or tremor	broad-based, unsteady gait, mildly increased limb tone	hypotonia, periodic abnormal posturing	n/k	limb hypertonia, positive Babinski sign and ankle clonus
Other features	constipation, abdominal pain, subtotal colectomy and ileostomy	left anterior temporal lobectomy and partial amygdalo-hippocampectomy	severe scoliosis	antenatal renal pelvic dilatation, recurrent UTI, nephrectomy	hypothyroidism	atrial septal defect	regression at 14 m

Variants based on transcript GenBank: NM_004114.5. Age in y(ears), m(onths), w(eeks), or d(ays); AED, antiepileptic drugs; ASD, autism spectrum disorder; EEG, electroencephalogram; EIMFS, epilepsy of infancy with migrating focal seizures; GTCS, generalized tonic-clonic seizures; ID/DD, intellectual disability or developmental delay; LGS, Lennox-Gastaut syndrome; NCSE, nonconvulsive status epilepticus; n/k, not known; SD, standard deviations; sz, seizures; UTI, urinary tract infection.

^aMaternal gonadal mosaicism is presumed in family A.